Autophagy & Phagocytosis in Neurological Disorders and their Possible Cross-talk

Abstract

Autophagy and phagocytosis are two important endogenous lysosomal dependent clearing systems in the organism. In some neurological disorders, excessive autophagy or dysfunctional phagocytosis has been shown to contribute to brain injury. Recent studies have revealed that there are underlying interactions between these two processes. However, different studies show inconsistent results for the contribution of autophagy to the phagocytic process in diverse phagocytes and relatively little is known about the link between them especially in the brain. It is critical to understand the role that autophagy plays in phagocytic process in order to promote the clearance of endogenous and exogenous detrimental materials. In this review, we highlight the studies focusing on phagocytosis and autophagy occurring in the brain and summarizing the possible regulatory roles of autophagy in the process of phagocytosis. Balancing the roles of autophagy and phagocytosis may be a promising therapeutic strategy for the treatment of some neurological diseases in the future.

Keywords: LC3 associated phagocytosis; Phagocytosis; autophagy; brain; cross-talk; interactions; microglia..

Fig. (1)

The major steps of phagocytosis: “find me”, “eat me”, and “digest me”. This figure shows dying cells as an example to depict the process of phagocytosis. Dying cells release “find me” signals to attract the migration of phagocytes. The attracted phagocytes recognize and tether the target through “eat me” signals. Next, the phagocytes engulf and internalize the cells via scavenger receptors.Finally, the phagosome fuses with lysosome and the formed phagolysosome which degrades the target. LPC: lysophosphatidylcholine; G2A:LPC receptor, also termed G-protein–coupled receptor 132(GPR132); S1P:sphingosine-1-phosphate; CX3CL1:CX3C motif chemokine ligand 1; CX3CR1: CX3C chemokine receptor 1;PtdSer: phosphatidylserine; Tim: T-cell immunoglobulin and mucin domain-containing molecule; BAI1: Brain-specific angiogenesis inhibitor 1; RAGE: Receptor for advanced glycation end products; LRP1: Low density lipoprotein receptor-related protein 1; MSR1: Macrophage scavenger receptor 1; MARCO: macrophage receptor with collagenous structure. (A higher resolution/colour version of this figure is available in the electronic copy of the article).